Scott Commins, MD, PhD, Associate Professor of Medicine & Pediatrics at the UNC Division of Rheumatology, Allergy, and Immunology talks about a mysterious meat allergy.
Interview conducted by Ivanhoe Broadcast News in October 2018.
Let’s start with, how did you come across this mystery meat allergy? How did this cross your path?
Dr. Commins: The background is that it actually started in the cancer world where patients were reacting on the first infusion of a new cancer medication. And by reacting I mean having anaphylaxis. They were having hives, itching, loss of blood pressure, loss of consciousness. And for us the really interesting aspect of that was that it was the first infusion. So those patients should not have had any antibody response that would have been directed against the new medication. In the process of figuring out that story, my boss at the time, Dr. Platts-Mills, developed a test for a sugar called alpha-gal. And it turns out that people can develop an allergic response to alpha-gal and this appears to be due to tick bites.
We found this initially in just a handful of folks in central Virginia who came to us with a story that went something like: “Look doc, I think I’m allergic to beef and maybe pork, and maybe lamb too. It doesn’t happen every time and what’s weird is that it happens in a delayed manner. So I eat a hamburger and then four or five hours later I get hives.” That was really paradigm shifting for us in the food allergy landscape. But the way this whole alpha-gal story unfolds is that we had this test that we developed related to a cancer drug and this detected an allergic response to alpha-gal. We were studying this sugar because of that work in the cancer world and it turns out that alpha-gal is a sugar found in all lower mammals. We thought that might explain why someone could be allergic to beef and pork and lamb. When we ran a blood test on those few patients for this new alpha-gal allergy it turns out they were positive. It started with literally five or six patients telling us that type of story and then it began to expand. In two 2009 we published the first series of twenty four patients. Nineteen from central Virginia and five from southern Missouri all reporting delayed allergic reactions to beef, pork or lamb.
And that was key — the delayed reaction — because when we think food allergies or other things that might give us a reaction, it happens immediately.
Dr. Commins: It happens immediately. You’re at the table and you know before you leave the restaurant, because someone put peanut or tree nut in your dish. This was a completely different story — they had no idea two hours after eating a hamburger, that in another two hours they’d be covered in hives and have severe itching.
I want to have you explain sort of the pathway of how this happened and how these ticks are involved. And the reactions can be as severe as anaphylactic shock?
Dr. Commins: That’s right. I don’t like the word shock but anaphylaxis absolutely. The severe allergic reaction where you could even have trouble breathing, your blood pressure can go quite low and we can see that in the setting of hives. But equally we see a group of these patients who report distinctly abdominal pain, GI cramping, maybe even nausea or vomiting, and may not get hives. It becomes a really difficult diagnosis to make if six hours after you eat a hamburger you get belly pain. You don’t think food allergy.
Right, you’re not connecting it with what you ate six hours ago. Explain how did you go from these people are having an allergic reaction, to how did the ticks come in, what kind of ticks are these, and what do they do?
Dr. Commins: Right, that’s a great question. And that was one of the big things we wondered is why were people all of a sudden, fifty, sixty year old people becoming allergic to beef, pork or lamb and through a series of steps what we have found out is that it appears to be generated, the allergy appears to be generated from tick bites. And one of the initial observations was as we began to raise awareness, that this was happening in allergy circles so to speak. We generated a map and we’re able to understand that the southeast was particularly affected and we had states where there were twenty five, fifty cases very quickly after the initial description. And when we compared that map to a map of the distribution of Rocky Mountain spotted fever it was very similar in terms of which states became hotspots. There were two serendipitous events which occurred and that was that two people within the lab developed the meat allergy themselves and in both instances it occurred following tick bites. That led us to ask the question, could tick bites be causing this. We had originally enrolled nearly two hundred subjects with meat allergy having no idea that ticks could have been the cause. We had to go back, phone them again, and take a history related to tick bites, and sure enough over ninety percent of them reported recent tick bites.
Over ninety percent, so the connection is these ticks and it’s a certain type of tick?
Dr. Commins: In the southeast it is primarily the lone star tick called Amblyomma americanum.
And ticks are found normally where?
Dr. Commins: They’re in the south of the United States and up the east coast. Actually now (they) have spread in to the Ohio River valley, and there are reports of these ticks as far north as Minnesota. So the geographic range of the lone star tick is expanding. And we’re seeing I think because of that an expansion of the cases of alpha-gal allergy.
That seems to be spreading as well, expanding across the country?
Dr. Commins: Correct.
How does that happen? Does the tick bite the animal and then the person gets bitten by the tick, and then how does that allergy react in the person’s body?
Dr. Commins: Our leading hypothesis is that the tick takes a blood meal off of a mammal, a lower mammal like a deer or a dog and then bites a human. During the blood meal from the deer or dog, the tick would come in contact and have alpha-gal because those animals have alpha-gal as a blood group substance. And when the tick bites a human it could logically sensitize us to alpha-gal that was retained in its salivary glands from the prior meal.
Also, this could happen to anyone: you never had an allergic reaction to meat before and you get bitten by a tick, and you then develop sensitivity to alpha-gal inform the tick’s saliva, then all of a sudden you have this meat allergy?
Dr. Commins: That’s right. It’s an excellent point because most of what we know in the allergy world and allergy clinics involves people who started with eczema and then had asthma and got allergic rhinitis. They have a history of being in our allergy clinics. This allergy breaks that pattern. In fact, we have patients in the fifth or sixth decade of life who would say, “I’ve never been to an allergist before, I don’t have hay fever, I don’t have asthma.” But they get bitten by the a tick and they end up with red meat allergy.
So it’s just by chance?
Dr. Commins: It appears to be by chance. We don’t know at this point whether the hypothesis about the blood meal from a deer or dog is correct. Or if perhaps the tick itself is carrying something that can sensitize humans just through feeding.
So that would mean that, that person gets a meat allergy essentially bitten by the tick they become allergic to that sugar alpha-gal.
Dr. Commins: That’s right. So that person then has an IgE which is the allergic antibody. They have IgE that recognizes this alpha-gal sugar.
And that reaction could be respiratory, it could be the hives, it could be itching.
Dr. Commins: And you and I have discussed mainly meat so far but if you think about it this also, and we know from patients, this crosses over frequently into dairy so it’s in products that are derived from mammals as well. Gelatin is just one example. Even bioprosthetic heart valves that come from pigs or cattle could potentially be an issue for some who have this allergy.
That could be a very serious issue.
Dr. Commins: Yes,
But we don’t know for sure yet.
Dr. Commins: Well we’ve seen people that have reacted but I think there is more to that story to come.
Not everyone then who is bitten by a tick carrying that alpha-gal has the reaction, correct?
Dr. Commins: That’s correct – that’s what we think at this time. We’re confident that not every tick bite leads to this. In fact, we are hard at work trying to figure out what I call the denominator. How many tick bites are there, how many does it take then to get one person who becomes allergic. I really think it’s a fraction of people who are bitten by ticks ever become actually allergic to red meat.
How many cases do you know of so far?
Dr. Commins: We’re confident of five thousand cases. I believe that’s an underestimate because the allergy often goes undiagnosed, but we know of at least that number of cases.
How are you testing this in the lab with the ticks?
Dr. Commins: We have been working hard on a mouse model because we can’t ask people to get tick bites. We have alpha-gal deficient mice – which don’t have alpha-gal in their biological make up. They, in that way, are kind of like humans. We don’t have alpha-gal. We then sensitize these alpha-gal deficient mice with tick salivary gland extract that we obtain from a collaborator. After several immunizations, these mice develop an IgE allergic antibody response to alpha-gal. And when treated with pork meat they develop an allergic reaction.
So—
Dr. Commins: What this model allows us to do is to be able to then feed ticks on different hosts, not just sheep but also perhaps a chicken which wouldn’t have alpha-gal or a reptile which similarly wouldn’t have alpha-gal and see if we can replicate the allergy. That would allow us to know whether that blood meal is really critical for the ticks to then cause the allergy. If we see that ticks fed on any animal can cause the allergy, then it makes us believe that there’s something about ticks saliva itself that can simply do this.
So this should help distinguish that part of it? How far are you guys on that research?
Dr. Commins: We are in the early stages, and we are moving forward.
At this point then what would you tell people to watch out for to protect themselves? You are saying these ticks are concentrated in one area of the US but it seems to be expanding.
Dr. Commins: It does seem to be expanding so if you’ve been bitten by a tick that you believe could be a lone star tick the first thing to do of course is to save the tick so we know what kind it was. But I wouldn’t make any alterations after the initial bite. People need to be aware of headaches, fevers, or joint pain, things that might alert them to a more traditional tick borne illness or infection. It’s really only after someone has a sense of an allergic response or GI upset, or even nausea hours after having a meal of beef or pork or lamb, rabbit, goat that type of thing, that we would do any kind of testing for the meat allergy.
So in terms of precautions, we often think about what the CDC has taught us. If you’re going to have to be outside or you want to be outside stick to the trails when you can. Particularly for lone star ticks which are moved around significantly by deer. Deer love to stand in the area between the fields and the forest, sort of that transition zone. If you can avoid that area it’s really helpful. Equally, wearing long pants and covering as well as possible, and using some DEET-related spray is also helpful, and being sure to do tick checks as quickly as possible after being in the woods.
And the unusual, even more unusual part of the thing is that sometimes you find these patients stop having the allergy.
Dr. Commins: Yes, so there is hope. In our group we have found that roughly twenty five to thirty percent of people will achieve complete resolution of this allergy often within the first two to three years. The caveat there is that additional tick bites seem as though they can perpetuate this and extend the time that folks are dealing with it. Our patients that are outdoorsy and frequently head in to the woods often have to adjust their diet for quite a long time.
And again this is not if you are elderly or have a low immune system that would make you more susceptible in a sense?
Dr. Commins: No, it doesn’t seem that age really plays a role. We have equal numbers of male and female patients with this. We have children as young as twenty months that have had it and folks as old as in their early eighties who have developed it.
And it is a food allergy, bottom line this is a food allergy?
Dr. Commins: This is a food allergy. Many of our patients carry epinephrine, particularly when they travel.
And where you are in your research doctor, what’s the next step or the goal?
Dr. Commins: The few things that keep me awake at night are trying to figure out exactly what it is about the tick bite that leads to this IgE response. Secondly, potentially does this involve more than tick bites? So could other insects that take blood meals also be involved? And then of course we all want a cure so we are working and thinking hard about the ways to be able to treat this allergy.
And if you can find out exactly what’s causing it specifically then that is the hope that you would be able to have a treatment.
Dr. Commins: Perfect, because what we do for people that have a bee sting allergy, or wasp or venom allergy is we give them allergy shots. So we’re hopeful if we can figure out what it is about the tick’s saliva that causes this then perhaps we could do a similar regimen of allergy shots geared at that tick salivary protein to try to desensitize folks over time.
If people wanted to learn more about this is there a place, is there a website?
Dr. Commins: We see patients at the UNC allergy clinic, and we are developing materials for a web presence as well.
And right now the people that you have found that have fallen ill with this food allergy it’s in the southeast region. We know it’s expanding.
Dr. Commins: It is expanding. Primarily the southeast but the east should not be discounted. We know of several hundred people on Long Island that have it. We also know globally that this is an issue. We collaborate with investigators in Europe and Southern Sweden and Australia, South Africa, thus it has really expanded geographically.
END OF INTERVIEW
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